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四逆散改善Mdr2^(-/-)小鼠胆汁淤积性肝纤维化作用

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药物评价研究 2024年第2期47卷 291-301页

作者：范桂芳蔡雅洁李方红李宇飞刘闰平北京中医药大学中药学院北京100029

目的研究四逆散对Mdr2(Abcb4)基因缺陷(Mdr2^(-/-))小鼠胆汁淤积性肝纤维化的缓解作用,并探究其作用机制。方法 C57BL/6J小鼠作为对照组;C57BL/6J背景的Mdr2^(-/-)小鼠作为模型小鼠,设模型组和四逆散低、高剂量(按生药量计为3.12、6.2... 详细信息

目的研究四逆散对Mdr2(Abcb4)基因缺陷(Mdr2^(-/-))小鼠胆汁淤积性肝纤维化的缓解作用,并探究其作用机制。方法 C57BL/6J小鼠作为对照组;C57BL/6J背景的Mdr2^(-/-)小鼠作为模型小鼠,设模型组和四逆散低、高剂量(按生药量计为3.12、6.24 g·kg^(-1))组。四逆散组连续3周ig给予四逆散水提物,每天1次,对照组给予纯水。试剂盒法检测血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆汁酸水平;取肝脏、脾脏称质量,计算肝脏、脾脏系数;结合小鼠肝组织HE染色,Masson染色,纤连蛋白(Fibronectin)、细胞角蛋白19(CK19)的免疫组化染色,明确四逆散对Mdr2^(-/-)小鼠肝纤维化及胆汁淤积的影响。基于小鼠肝脏转录组学测序技术,挖掘四逆散改善Mdr2^(-/-)小鼠肝损伤的作用靶点,并通过实时荧光定量PCR(qRT-PCR)法检测肝纤维化[fibronectin(Fn1)、胶原蛋白1(Col1a1)、角蛋白19(krt19)]、炎症[白细胞介素-1β(Il1β)、Il6、肿瘤坏死因子-α(Tnfα)、一氧化氮合成酶(Inos)]、细胞焦亡[凋亡相关斑点样蛋白(Pycard)、Il18]、胆汁酸合成[细胞色素P450家族成员7A1(Cyp7a1)]及转运[胆盐输出泵(Abcb11)、ATP结合盒转运蛋白(Abcc3)、钠离子-牛磺胆酸共转运蛋白(Slc10a1)]相关基因的转录水平。结果与模型组比较,四逆散高剂量显著降低血清总胆汁酸的水平(P<0.05);明显缓解了Mdr2^(-/-)小鼠肝脏中央静脉及胆管周围炎性细胞的浸润和胶原纤维的沉积,并显著抑制胆管反应的发生。转录组学及qRT-PCR结果共同表明,四逆散下调Mdr2^(-/-)小鼠肝脏纤维化、炎症、细胞焦亡相关基因的转录(P<0.05);同时,四逆散下调胆汁酸合成关键限速酶调控基因Cyp7a1和调控胆汁酸向肝内转运的基因Slc10a1的转录,并上调调控胆汁酸外排的基因Abcb11、Abcc3的转录。结论四逆散能缓解Mdr2^(-/-)小鼠胆汁淤积性肝纤维化,机制可能与其调控炎症反应、细胞焦亡以及胆汁酸的合成和转运有关。

关键词：四逆散胆汁淤积性肝纤维化转录组学炎症细胞焦亡胆汁酸代谢

多维驱动下“三位一体”新工科创新型人才协同聚力培养

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高教学刊 2024年第1期10卷 47-50页

作者：邵桂芳杨帆王颖刘暾东文玉华厦门大学航空航天学院福建厦门361102

鉴于当前研究生教育存在学科壁垒导致的牢笼化培养,难以满足高端创新人才的社会需求,团队从学术氛围营造、多维能力培养及协同融合等三个方面探索新工科创新人才培养机制。提出开放共享学术生态环境构建策略,以学生为中心,融合多种方案... 详细信息

鉴于当前研究生教育存在学科壁垒导致的牢笼化培养,难以满足高端创新人才的社会需求,团队从学术氛围营造、多维能力培养及协同融合等三个方面探索新工科创新人才培养机制。提出开放共享学术生态环境构建策略,以学生为中心,融合多种方案,建立学生志趣与社会需求、应用能力与理论创新的多样化与个性化协同的阶梯式个性化综合素质培养模式,以及项目驱动的校企合作平台协同育人机制,并给出实际应用案例与培养成效。

关键词：创新型人才新工科协同教育多维驱动产学研协同

RR-1 cuticular protein TcCPR69 is required for growth and metamorphosis in Tribolium castaneum

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Insect Science 2022年第6期29卷 1612-1628页

作者： Jia Xie guifang Peng Miao Wang Qisheng Zhong Xiaowen Song Jingxiu Bi Jing Tang fan Feng Han Gao Bin Li Jiangsu Key Laboratory of Biodiversity and Biotechnology College of Life SciencesNanjing Normal UniversityNanjingChina Key Laboratory of Green Prevention and Control of Tropical Plant Diseases and Pests Ministry of EducationCollege of Plant Protection HainanUniversityHaikouChina

Cuticle is not only critical for protecting insects from noxious stimuli but is also involved in a variety of metabolic activities.Cuticular proteins(CPs)affect cuticle structure and mechanical properties during insect growth,reproduction,and environmental adaptation.Here,we describe the identification and characterization of a member of the RR-1 subfamily of CPs with an R&R consensus(CPR)in Tribolium castaneum(TcCPR69).Although it was previously reported to be highly expressed in the wings,we found that knocking down TcCPR69 by RNA interference(RNAi)did not cause obvious wing abnormalities but markedly disrupted the growth and metamorphosis of beetles with 100%cumulative mortality;additionally,the chitin content of the pharate adult was decreased and the new abdominal cuticle was significantly thinner before molting.TcCPR69 showed chitin-binding ability and the expression levels of key genes involved in chitin metabolism(trehalase[TcTRE],chitin synthase[TcCHSA and TcCHSB],and chitinase[TcCHT5 and TcCHT10])were also decreased by TcCPR69 knockdown.TcCPR69 gene expression peaked shortly after molting and was increased 2.61 fold at 12 h after 20-hydroxyecdysone(20E)injection.This was reversed by RNAi of the ecdysone-related genes ecdysone receptor(TcECR)and fushi tarazu transcription factor 1(TcFTZ-F1).These results indicate that TcCPR69 is positively regulated by 20E signaling to contribute to cuticle formation and maintain chitin accumulation during the growth and metamorphosis of beetles.

关键词： chitin accumulation cuticle protein development 20-hydroxyecdysone molting RNA interference

Revisiting Electrolyte Kinetics Differences in Sodium Ion Battery:Are Esters Really Inferior to Ethers?

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Energy & Environmental Materials 2023年第4期6卷 203-210页

作者： Lei Yan guifang Zhang Jing Wang Qingjuan Ren Linlin fan Binhua Liu Yujia Wang Wenhua Lei Dianbo Ruan Qingyin Zhang Zhiqiang Shi Tianjin Key Laboratory of Advanced Fibers and Energy Storage School of Materials Science and EngineeringTiangong UniversityTianjin 300387China Institute of Advanced Energy Storage Technology and Equipment Ningbo UniversityNingbo Zhejiang 315211China School of Chemical Engineering and Technology Tiangong UniversityTianjin 300387China

The ether electrolytes usually outperform ester electrolytes by evaluating sodium-ion batteries(SIBs)rate performance,which is a near-unanimous conclusion of previous studies based on an essential configuration of the half-cell test.However,here we find that contrary to consensus,the ester electrolyte shows better Na storage capability than the ether electrolyte in full cells.An in-depth analysis of three-electrode,symmetric cell,and in situ XRD tests indicates that traditional half-cell test results are unreliable due to interference from Na electrodes.In particular,Na electrodes show a huge stability difference in ester and ether electrolytes,and ester electrolytes suffer more severe interference than ether electrolytes,resulting in the belief that esters are far inferior to ether electrolytes.More seriously,the more accurate three-electrode test would also suffer from Na electrode interference.Thus,a“corrected half-cell test”protocol is developed to shield the Na electrode interference,revealing the very close super rate capability of hard carbon in ester and ether electrolytes.This work breaks the inherent perception that the kinetic properties of ester electrolytes are inferior to ethers in sodium-ion batteries,reveals the pitfalls of half-cell tests,and proposes a new test protocol for reliable results,greatly accelerating the commercialization of sodium-ion batteries.

关键词： corrected half-cell test electrolyte kinetic data hard carbon Na electrode interference sodium-ion batteries

Cassiae Semen improves non-alcoholic fatty liver disease through autophagy-related pathway

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Chinese Herbal Medicines 2023年第3期15卷 421-429页

作者： Mingning Ding Fei Zhou Yijie Li Chuanyang Liu Yiqing Gu Jianzhi Wu guifang fan Yajing Li Xiaojiaoyang Li School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China

Objective:Cassiae Semen(CS,Juemingzi in Chinese)has been used for thousands of years in ancient Chinese history for relieving constipation,improving liver function as well as preventing myopia.Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease(NAFLD).Methods:High-performance liquid chromatography(HPLC)was used to identify the major components of CS water extract.Mice were fed with a high-fat and sugar-water(HFSW)diet to induce hepatic steatosis and then treated with CS.The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining.Additionally,the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid(OAPA)-treated HepG2 cells were measured.The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism.Results:Five compounds,including aurantio-obtusin,rubrofusarin gentiobioside,cassiaside C,emodin and rhein were simultaneously identified in CS extract.CS not only improved the diet-induced hepatic steatosis in vivo,as indicated by decreased number and size of lipid droplets,hepatic and serum triglycerides(TG)levels,but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes.These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase(FASN)and the activation of autophagy-related signaling,including AMP-activated protein kinase(AMPK),light chain 3-II(LC3-II)/LC3-1 and autophagy-related gene5(ATG5).Conclusion:Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy,which might become a promising therapeutic strategy for relieving NAFLD.

关键词： autophagy AMPK Cassia obtusifolia L. Cassia tora L. Cassiae Semenfatty acid synthesis non-alcoholic fatty acid disease

High flux photocatalytic self-cleaning nanosheet C_(3)N_(4) membrane supported by cellulose nanofibers for dye wastewater purification

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Nano Research 2021年第8期14卷 2568-2573页

作者： Lilong Zhang Ge Meng guifang fan Keli Chen Yulong Wu Jian Liu Institute of Nuclear and New Energy Technology Tsinghua UniversityBeijing 100084China The Key Laboratory of Bionic Engineering(Ministry of Education) Jilin UniversityJilin 130012China Department of Chemistry Tsinghua UniversityBeijing 100084China School of Chemical Engineering and Technology Xinjiang UniversityUrumqi 830046China College of Materials Science and Engineering Qingdao University of Science and Technology Qingdao 266042China

Hazardous dye substances discharged from the textile and dyestuff industries not only threaten local the surrounding ecosystems but are also hard to degraded.We report the preparation of process for a photocatalytic membrane device that can degrade dye pollution under visible light.This filtration membrane,with a well-organized multilayer structure,simultaneously achieves continuous and flow-through separation of degradation products.Cellulose nanofibers(CNFs)were used as a template for nanosheet C_(3)N_(4)(NS C_(3)N_(4))preparation;the performance for the photocatalytic degradation of dyes improved as the morphology changed from bulking to nanosheet.NS C3N4 was then attached to the surface of a prepared CNF membrane via vacuum filtration.This device exhibited high efficiency(the degradation rates of both Rhodamine B and Methylene blue both reached 96%),high flux(above 160 L·h^(-1)·m^(-2)·bar^(-1))and excellent stability(maintaining steady flux and high separation were maintained after 4 h).This easy-preparation,easy-scale-up,and low-cost process provides a new method of fabricating photocatalytic membrane devices for dye wastewater treatment.

关键词： high flux nanofibers nanosheet C_(3)N_(4) photocatalytic membrane dye wastewater

Performances of an air thermal energy utilization system developed with fan-coil units in large-scale plastic tunnels covered with external blanket

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International Journal of Agricultural and Biological Engineering 2022年第5期15卷 56-62页

作者： Chengji Zong Zibin Xiao Weitang Song Pingzhi Wang guifang Zhang Ming Li College of Water Resources and Civil Engineering China Agricultural UniversityBeijing 100083China Yinchuan Xingqing District Agricultural Technology Extension Center Yinchuan750001China Key Laboratory of Agricultural Engineering in Structure and Environment Ministry of Agriculture and Rural AffairsBeijing 10008

To improve the problem of low temperature at night in winter due to the lack of thermal storage in large-span plastic tunnels,an air thermal energy utilization system(ATEUS)was developed with fan-coil units to heat a large-scale plastic tunnel covered with an external blanket(LPTEB)on winter nights.The ATEUS was composed of nine fan-coil units mounted on top of the LPTEB,a water reservoir,pipes,and a water circulation pump.With the heat exchange between the air and the water flowing through the coils,the thermal energy from the air can be collected in the daytime,or the thermal energy in the water can be released into the LPTEB at night.On sunny days,the collected thermal energy from the air in the daytime(E_(c))and released thermal energy at night(E_(r))were 0.25-0.44 MJ/m^(2) and 0.24-0.38 MJ/m^(2),respectively.Used ATEUS as a heating system,its coefficient of performance(COP),which is the ratio of the heat consumption of LPTEB to the power consumption of ATEUS,ranged from 1.6-2.1.A dynamic model was also developed to simulate the water temperature(T_(w)).Based on the simulation,E_(c) and E_(r) on sunny days can be increased by 60%-73%and 38%-62%,respectively,by diminishing the heat loss of the water reservoir and increasing the indoor air temperature in the period of collecting thermal energy.Then,the COP can reach 2.6-3.8,and the developed ATEUS can be applied to heating the LPTEB in a way that conserves energy.

关键词： large scale plastic tunnel air thermal energy utilization system energy conservation COP

Establishment of Chlamydomonas reinhardtii chloroplast expression

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Chinese Science Bulletin 1999年第18期44卷 1659-1664页

作者： Guochang fan Ning Su Zhonglin Zhang Xiangfu Wu guifang Shen Chinese Acad Agr Sci Biotech Res Ctr Beijing 100081 Peoples R China Beijing Inst Radiat Med Beijing 100850 Peoples R China Chinese Acad Sci Shanghai Inst Biochem Shanghai 200031 Peoples R China

An expression vector pACⅢ containing the chimeric gene HAV- VP3P1 and HCV-C gene has been constructed and transferred to C. reinhardtii by the biolistic method. The trans-formants have been identified by PCR, Southern-blotting, Northern-blotting and Western-blotting assays after selecting on resistant medium and incubating in the dark. The results

关键词： HAV-VP3P1 gene HCV-C gene C. reinhardtii chloroplast expression system homologous recombinant.

Dual-enzyme-propelled unbounded DNA walking nanomachine for intracellular imaging of lowly expressed microRNA

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Nano Research 2019年第5期12卷 1055-1060页

作者： Tianshu Chen Yaoyao Chen Huinan Chen fan Zhang Qianqian Zhang guifang Chen Xiaoli Zhu Center for Molecular Recognition and Biosensing School of Life SciencesShanghai UniversityShanghai 200444China Institute of Biomedical Engineering School of Communication and Information EngineeringShanghai UniversityShanghai 200444China Department of Bioengineering University of WashingtonSeattleWA 98195USA

Despite the progress on the analysis of miRNA either in vitro or in vivo,intracellular imaging of lowly expressed microRNA remains a challenge.Here we develop a novel dual-enzyme-propelled DNA walking nanomachine,which is tailored to accomplish this mission.The nanomachine is constructed with nanoparticles-loaded DNA tracks,on which the targeted miRNA working as a single-foot DNA walker can move autonomously under the catalysis of two cooperative enzymes.Cleavage of the DNA tracks like a "burnt-bridge" mechanism is thereafter triggered,resulting in an amplified fluorescent signal.After the comprehensive study and optimization of the DNA nanomachine,miR-892b,a significantly down-regulated miRNA in breast cancer cells,is selected as a model target.Sensitivity detection in vitro is achieved with a superior detection limit of 4 pM.While being delivered into cells,the DNA nanomachine is available for the imaging of the lowly expressed microRNA,which is totally missing using the conventional fluorescence in situ hybridization (FISH) method.Up-regulation or down-regulation of the miRNA by exogenous regulatory factors can be also well evaluated.This DNA nanomachine provides a competitive approach for the analysis of miRNA,and has the potential to be extended to some other biomolecules.

关键词： DNA walker nanomachine microRNA nanoparticles imaging analysis